ALK-rearranged adenocarcinoma transformed to small-cell lung cancer: a new entity with specific prognosis and treatment?

Per Med. 2018 Mar;15(2):111-115. doi: 10.2217/pme-2017-0069. Epub 2018 Jan 30.

Abstract

Driving molecular mutations such as rearrangement of ALK and EGFR mutation is present in 5-10% of non-small-cell lung cancer. Tyrosine kinase inhibitors have shown good efficacy and thus become the standard of care. However, tumors have developed several resistance mechanisms against tyrosine kinase inhibitors, including transformation to small-cell lung carcinoma (SCLC). Transformation to SCLC after administration of anti-EGFR in EGFR-mutated adenocarcinoma has been well documented. Similarly, it appears that the same transformation happens in ALK-rearranged adenocarcinoma after the use of anti-ALK. In fact, to date eight cases have been reported in the literature. We aimed in this paper to focus on the characteristics, prognosis and treatment of these transformed SCLC.

Keywords: ALK rearrangement; adenocarcinoma; small-cell lung cancer transformation; treatment and prognosis.

MeSH terms

  • Adenocarcinoma / genetics
  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gene Rearrangement / drug effects
  • Gene Rearrangement / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazoles / pharmacology
  • Pyridines / pharmacology
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Small Cell Lung Carcinoma / genetics*

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases